There are an estimated 500,000 patients in the United States who develop bacteremia, with mortality rates ranging from 25-50%.1 Early recognition and aggressive therapeutic intervention is known to significantly improve outcomes for those with systemic bacterial infections.1 Unfortunately, no definitive clinical parameters or diagnostic assays currently exist that allow clinicians to rapidly and accurately identify patients with bacterial infections among those in whom systemic infections are suspected.
Patients with fulminant bacteremia are usually easily recognized by the presence of fever and significant vital sign abnormalities, described as sepsis syndrome. Early synthetic bacterial infections, or those which occur in vulnerable or immunosuppressed hosts may be more subtle however, leading to potential delays in diagnosis and treatment with associated increased risk for morbidity and mortality. Further, inherent limitations of the ‘gold standard’ diagnostic test for bacteremia, blood culture, renders it ineffective for guiding acute management decisions. These limitations include significant time delays associated with reporting of positive findings (typically at least 24-48 hours), relatively low sensitivity ranging from 30-50% among patients who meet criteria for sepsis syndrome, and diminished sensitivity in patients already on antibiotics.
The failure of either clinical judgment or diagnostic technology to provide quick and accurate data for identifying patients with bacteremia, leads most clinicians to follow a conservative management approach for those in whom systemic infection is suspected. Empiric intravenous antibiotic therapy offers the advantage of maximizing patient safety and improving outcomes for those later found to be bacteremic. Well known clinical examples in which patients are routinely hospitalized and given antibiotics while awaiting blood culture results include febrile episodes in infants, due to the high mortality associated with unrecognized septicemia, and any febrile illness in intravenous drug users due to the high risk of life-threatening infective endocarditis which is principally characterized by the presence of bacteremia. The benefits of conservative management may be offset however, by added costs and potential iatrogenic complications associated with treatment and hospital days for those later found not to be bacteremic, as well as increased rates of antimicrobial resistance. A rapid accurate assay for blood-borne bacterial infections which could be used to screen patients considered at risk would thus be invaluable for clinicians.
PCR, or polymerase chain reaction, is a technique which allows for rapid nucleic acid amplification and detection of small amounts of a target pathogen (e.g. bacterial RNA or DNA). Development of PCR diagnostics for clinical use have shown promise when primers for a specific pathogen are used in selected clinical settings. Examples include detection of Mycobacterium tuberculosis in patients with suspicious pulmonary infections, and identification of Streptococcus pneumoniae in children and infants with suspected septicemia from this organism. Numerous investigations have also been carried out employing a universal probe for more broad based bacterial identification. Findings published to date have principally been restricted to detection of bacteria in highly infected tissue specimens, e.g. resected heart valves in patients with suspected infective endocarditis, or clinical samples from an infected site such as an abscess. Unfortunately, less success has occurred with universal screening of blood samples, principally due to technical problems of the assay, most commonly related to contaminant bacterial DNA.
There is a need in the art for a rapid and sensitive test for detecting specific pathogens in clinical samples.